Adverse reactions of Everolimus

1. Clinical Trial Experience

Breast Cancer (BOLERO-2 Study)

Most common (≥30%) adverse reactions: Stomatitis, infection, rash, fatigue, diarrhea, decreased appetite.

Most common (≥2%) Grade 3-4 adverse reactions: Stomatitis, infection, hyperglycemia, fatigue, dyspnea, pneumonia, diarrhea.

Most common (≥50%) laboratory abnormalities: Hypercholesterolemia, hyperglycemia, elevated AST, anemia, leukopenia, thrombocytopenia, lymphopenia, elevated ALT, hypertriglyceridemia.

Permanent discontinuation rate: 24%; Dose adjustment rate: 63%.

Pancreatic Neuroendocrine Tumors (RADIANT-3 Study)

Most common (≥30%) adverse reactions: Stomatitis, rash, diarrhea, fatigue, edema, abdominal pain, nausea, fever, headache.

Most common (≥5%) Grade 3-4 adverse reactions: Stomatitis, diarrhea.

Permanent discontinuation rate: 20%; Dose delay or reduction rate: 61%.

Gastrointestinal or Pulmonary Neuroendocrine Tumors (RADIANT-4 Study)

Common adverse reactions (incidence ≥10% with absolute incidence ≥5% higher than placebo, or Grade 3-4 incidence ≥2% higher than placebo): Stomatitis, diarrhea, nausea, vomiting, peripheral edema, fatigue, asthenia, fever, infection, weight loss, decreased appetite, dysgeusia, cough, dyspnea, pneumonia, epistaxis, rash, pruritus.

Permanent discontinuation rate: 29%; Dose reduction or delay rate: 70%.

Renal Cell Carcinoma (RECORD-1 Study)

Most common (≥30%) adverse reactions: Stomatitis, infection, asthenia, fatigue, cough, diarrhea.

Permanent discontinuation rate: 14%.

TSC-Associated Renal Angiomyolipoma (EXIST-2 Study)

Most common (≥30%) adverse reaction: Stomatitis.

Permanent discontinuation rate: 3.8%; Dose adjustment rate: 52%.

TSC-Associated Subependymal Giant Cell Astrocytoma (SEGA) (EXIST-1 Study)

Most common (≥30%) adverse reactions: Stomatitis, respiratory tract infection.

Permanent discontinuation: None; Dose adjustment rate: 55%.

TSC-Associated Partial Seizures (EXIST-3 Study)

Most common (≥30%) adverse reaction: Stomatitis.

Study drug discontinuation rate: 5% (low trough concentration group), 3% (high trough concentration group); Dose adjustment rate: 24% (low trough concentration group), 35% (high trough concentration group).

Local Prevention of Stomatitis (SWISH Study)

Concurrent use of alcohol-free dexamethasone mouthwash at treatment initiation reduced the incidence of Grade 2-4 stomatitis from 33% (in BOLERO-2) to 2% within 8 weeks.

2. Postmarketing Experience

Voluntarily reported adverse reactions include: Thrombotic microangiopathy, heart failure with pulmonary hypertension, acute pancreatitis, cholecystitis and cholelithiasis, sepsis and septic shock, reflex sympathetic dystrophy, arterial thrombotic events, lymphedema, radiation sensitization, and radiation recall.

FDA，2022.02